Severe Epistaxis Secondary to Dabrafenib and Trametinib Toxicity in Non-small Cell Lung Carcinoma With Small Bowel Metastasis.

ABSTRACT

BRAF mutations are estimated to be present in 2-4% of non-small cell lung carcinoma (NSCLC) cases. BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) are currently approved to treat NSCLC harboring the BRAF V600E mutation. However, the use of this new combined targeted therapy can be associated with severe and life-threatening toxicities. Here, we describe the case of a 77-year-old male with a history of BRAF-positive lung adenocarcinoma with metastasis to the brain, adrenals, and small bowel (jejunum), currently on dual therapy with dabrafenib and trametinib, who presented with refractory epistaxis. The dual therapy regimen was started one month prior to his presentation. After initial stabilization with anterior nasal packing, intravenous and nebulized tranexamic acid (TXA) in the emergency department (ED), he suddenly developed respiratory decompensation. He needed emergent intubation for acute hypoxic respiratory failure and airway protection secondary to profuse bleeding. He was extubated 24 hours later as the epistaxis was manageable, and the nasal packing was removed. Shortly after extubating, he started coughing copious amounts of blood and developed respiratory distress with stridor requiring re-intubation. A large blood clot was noted to be partially occluding the vocal cords on laryngoscopy and was removed during intubation. An emergent flexible fiberoptic bronchoscopy was performed with the retrieval of a large blood clot extending from the oropharynx down into the distal trachea. There was no evidence of acute bleeding within the lung after the clot was removed. Workup to explore the cause of his bleeding included a coagulation profile, which was unrevealing. His bleeding was most likely consistent with a side effect of his treatment with dabrafenib and trametinib. Life-threatening bleeding has been reported as a side effect of the combination therapy with dabrafenib and trametinib in metastatic melanoma. Also, in the phase 2 clinical trial (BRF113928) of dabrafenib plus trametinib in patients with previously untreated BRAF V600E-mutant metastatic NSCLC, 3.2% of subjects developed a grade III or IV hemorrhage. Our case aims to raise physicians' awareness of one of the significant side effects of this combination therapy especially since this combination is being used more frequently and now also in lung cancer.